Project Summary/Abstract The negative consequences of pediatric bipolar disorder (BP) are well documented, but the course, outcome, and prognostic factors of BP as youth transit into adulthood remain unknown. To answer these questions, the Predicting Adult Outcomes in BP Youth (PROBY), a multisite study (University of Pittsburgh, PI: B.Birmaher; Brown University, PIs: M.Keller/S.Yen; UCLA, PI: M.Strober), proposes: 1) to extend the prospective follow-up of the Course and Outcome of Bipolar Youth (COBY) cohort into adulthood, and 2) to use COBY data to build risk calculators to predict short-(2 years), intermediate-(5 years), and long-term (10 years) personalized mood course/outcome that capture transitions from adolescence through adulthood. We will study five key domains relevant for BP: 1) course of mood and non-mood disorders; 2) psychosocial functioning; 3) suicidality; 4) SUD; and 5) cognitive functioning. Risk calculation is an analytic approach that instead of group prediction, yields individualized estimates of risk for a specified event in a given patient, based on the presence of multiple risk factors. The risk calculators proposed in PROBY will have a true population impact by predicting BP outcomes, similar to those used in cardiovascular disease and cancer, but rarely applied in psychiatric disorders. The risk calculators will include well-established variables, in order to allow replication and clinical utility. Also, these variables are easily ascertained in clinical settings and are part of standard practice and thus, will be widely disseminable, and hold promise for utility in daily clinical practice. For example, results may be used to: counsel patients/families about long-term prognosis; individualize treatment by identifying patients likely to require prolonged treatments and those for whom medications may be reduced with minimal risk; and inform early intervention/prevention and clinical/biological research. To pursue the proposed study, 343 COBY subjects (BP-I=72.3%, BP-II=14.6%, BP-NOS=13.1%, mean age 26.3 (18.7?33.7), 47% female, 82% Caucasian, and on average, middle class), will have 2 additional clinical assessments over the five years of study. These subjects represent 77% of the original sample (n=446) enrolled between 2000 and 2006 at the three study sites. PROBY will continue to prospectively collect data on categorical and dimensional psychopathology, protective factors, psychosocial functioning (e.g., relationships, work, academics), cognitive functioning, inflammatory markers, cardiometabolic conditions, exposure to stressful/traumatic life events, and treatment (e.g., medication dosages, barriers). With 5 additional years of prospective observation, the mean age of the sample will be 31.3 years old (23.7?38.7). Thus, PROBY will be the first study with adequate sample size to answer questions about what happens to BP youth when they grow up. Furthermore, PROBY will be the first study to build risk calculators to predict outcome in key domains relevant for BP and validate these results using an independent adult BP sample (n=427) from the Collaborative Depression Study (CDS; R01 MH025416). These risk calculators have the potential to widely transform clinical care of BP.